The purpose of the research program outlined in this proposal is to increase our understanding of the organization of synapses in the brain. Increased knowledge of the structure and function of synapses is necessary before we can understand the alterations of these in development and in diseases of the brain, such as mental retardation, epilepsy, and psychoses. The specific studies planned continue a combined analysis of synapse morphology, spatial relations and localization of putative neurochemical transmitter substances in the anteroventral nucleus of the thalamus, interpeduncular nucleus and suprachiasmatic nucleus, all in albino rats. Analysis of the normal morphology of these nuclei after perfusion fixation with osmium tetroxide and aldehyde solutions serves as a basis for the other studies. Lesions in the major areas projecting to these nuclei, short survival periods and electron microscopic examination will allow by recognition of degenerative changes an analysis of the sources of the various groups of synapses in these nuclei. These observations will be confirmed and extended by demonstration of axoplasmic tranport of radioactive amino acids from the same areas of projection. The autoradiographic demonstration of the uptake of radioactive labelled putative neurochemical transmitters into brain slices in vitro will be correlated with synapse fine structure and source. The appearance of these synaptic relations in development will be demonstrated at selected early life stages. This detailed analysis of multiple aspects of synaptic relationships in these selected sites, when combined with physiological and pharmacological concepts will allow new insight into synaptic function.